We will synthesize a small library of heptapeptide scaffolds to explore the effects of scaffold conformation on cyclization and cell permeability. We will select several novel cell-permeable cyclic scaffolds for elaboration into libraries of potential protein ligands and screen them for effects on the cell cycle in a number of different assays. Several active compounds will be chosen for further study. We are particularly interested in compounds that arrest cells in mitosis by directly perturbing the degradation of cyclin B or by targeting components of the mitotic spindle and thus triggering the mitotic checkpoint pathway.